The invention relates to an insertable, miniature x-ray source for intravascular irradiation following percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease.
Coronary artery disease is currently the leading cause of death in the United States. In coronary artery disease, fatty deposits called plaque accumulate on the walls of the coronary arteries. These deposits cause stenosis (narrowing of the lumen) and, in advanced cases, can cause complete occlusion of the artery leading to myocardial infarction and possibly death. The most widely used and successful treatment for coronary artery disease is balloon angioplasty, a procedure in which a deflated balloon is passed through a catheter to the site of an arterial stenosis and inflated to compress the plaque deposits and restore the patency of the lumen. While balloon angioplasty has a very high rate of success in terms of opening the lumen, 40-60 % of patients suffer restenosis at the site of the angioplasty within 6 months of the procedure. The mechanism of restenosis is thought to be the abnormal proliferation of injured smooth muscle cells at the treatment site, resulting in neointima formation and renarrowing of the lumen.
Animal and early clinical studies have shown that irradiation of the arterial wall to a dose of 15-20 Guy following PTCA has the effect of preventing or significantly delaying restenosis. Irradiations to date have been performed using external x-ray beams or radioactive sources. External beams have the disadvantage that radiation dose is delivered to a large volume of healthy tissue concurrent with dose delivery to the treatment site. Radioactive sources, on the other hand, can be guided to the treatment site via the same arterial catheter used to position the angioplasty balloon, making possible localized dose delivery. Vascular brachytherapy using the gamma emitter .sup.192 Ir or the .beta..sup.- -emitters 32P, .sup.90 Sr, .sup.90 Y, .sup.166 Ho, or .sup.188 Re is being investigated by several research groups. These radioisotopes have half-lives of fourteen days to twenty-seven years and radiation penetration depths in tissue of approximately three millimeters to several centimeters.
The use of radioactive sources for vascular brachytherapy suffers several significant drawbacks. First, because therapy must be delivered within a short time window, high radioisotope activities in the range 50-200 mCi are required. Thus, extreme care must be taken to insure that insertion and withdrawal of the source are sufficiently rapid that dose delivered to other parts of the artery are within acceptable limits, and that the entire radioactive source is withdrawn intact from the patient. Handling of the source by physicians and other hospital personnel must be minimized and strict controls must be instituted to insure safe storage when not in use. In the case of the high energy gamma emitter .sup.192 Ir for example, the patient must be isolated and the source inserted through an automated catheter afterloader to prevent unacceptable dose to other personnel in the catheter laboratory. This procedure is clearly not compatible with usual practice during coronary catheterization in which the interventional cardiologist and other staff work in close proximity to the patient. When beta-emitters are used, isolation of the patient is not required because of the relatively short range of the .beta. radiation, but storage, handling, and periodic replacement of sources is still required.
In addition to the practical drawbacks described above, radioactive sources are limited in their dosimetric characteristics. Each radioisotope has a dose vs. depth profile which is fixed by the types and energies of its radioactive emissions. Thus, the dose profile cannot be adjusted to meet the requirements of a particular treatment scenario.
International application PCT/US96/13629 published Mar. 6, 1997 discloses an electronic x-ray catheter that is small and flexible enough to access an intended site within a vascular system of the body, such as the coronary arteries of the cardiovascular system. The catheter includes a flexible catheter shaft having a distal end and an electronic x-ray unit coupled to the distal end. The electronic x-ray unit comprises an anode, a cathode and an insulator that define a vacuum. A problem with this x-ray unit is that the insulating material extends into an x-ray aperture through which x-rays escape from the unit. The presence of the insulator constrains the dose depth profile that can be produced by the unit. In addition, extending the insulator into the region radially surrounding the gap between anode and the cathode can lead to an eventual breakdown of the insulator. This is because the insulator will be exposed to charged particles and neutral particles produced in the gap between the anode and the cathode. Furthermore, the geometry disclosed in this published application establishes electric field lines which can lead to insulator breakdown due to charged particles from the anode following the field lines to the insulator.
Therefore, there is a need for an improved miniature x-ray unit and techniques for irradiating an arterial wall.